Inferring Geodesic Cerebrovascular Graphs: Image Processing, Topological Alignment and Biomarkers Extraction

A vectorial representation of the vascular network that embodies quantitative features - location, direction, scale, and bifurcations - has many potential neuro-vascular applications. Patient-specific models support computer-assisted surgical procedures in neurovascular interventions, while analyses on multiple subjects are essential for group-level studies on which clinical prediction and therapeutic inference ultimately depend. This first motivated the development of a variety of methods to segment the cerebrovascular system. Nonetheless, a number of limitations, ranging from data-driven inhomogeneities, the anatomical intra- and inter-subject variability, the lack of exhaustive ground-truth, the need for operator-dependent processing pipelines, and the highly non-linear vascular domain, still make the automatic inference of the cerebrovascular topology an open problem. In this thesis, brain vessels’ topology is inferred by focusing on their connectedness. With a novel framework, the brain vasculature is recovered from 3D angiographies by solving a connectivity-optimised anisotropic level-set over a voxel-wise tensor field representing the orientation of the underlying vasculature. Assuming vessels joining by minimal paths, a connectivity paradigm is formulated to automatically determine the vascular topology as an over-connected geodesic graph. Ultimately, deep-brain vascular structures are extracted with geodesic minimum spanning trees. The inferred topologies are then aligned with similar ones for labelling and propagating information over a non-linear vectorial domain, where the branching pattern of a set of vessels transcends a subject-specific quantized grid. Using a multi-source embedding of a vascular graph, the pairwise registration of topologies is performed with the state-of-the-art graph matching techniques employed in computer vision. Functional biomarkers are determined over the neurovascular graphs with two complementary approaches. Efficient approximations of blood flow and pressure drop account for autoregulation and compensation mechanisms in the whole network in presence of perturbations, using lumped-parameters analog-equivalents from clinical angiographies. Also, a localised NURBS-based parametrisation of bifurcations is introduced to model fluid-solid interactions by means of hemodynamic simulations using an isogeometric analysis framework, where both geometry and solution profile at the interface share the same homogeneous domain. Experimental results on synthetic and clinical angiographies validated the proposed formulations. Perspectives and future works are discussed for the group-wise alignment of cerebrovascular topologies over a population, towards defining cerebrovascular atlases, and for further topological optimisation strategies and risk prediction models for therapeutic inference. Most of the algorithms presented in this work are available as part of the open-source package VTrails

Automatic analysis of retinal images to aid in the diagnosis and grading of diabetic retinopathy

Diabetic retinopathy (DR) is the most common complication of diabetes mellitus and one of the leading causes of preventable blindness in the adult working population. Visual loss can be prevented from the early stages of DR, when the treatments are effective. Therefore, early diagnosis is paramount. However, DR may be clinically asymptomatic until the advanced stage, when vision is already affected and treatment may become difficult. For this reason, diabetic patients should undergo regular eye examinations through screening programs. Traditionally, DR screening programs are run by trained specialists through visual inspection of the retinal images. However, this manual analysis is time consuming and expensive. With the increasing incidence of diabetes and the limited number of clinicians and sanitary resources, the early detection of DR becomes non-viable. For this reason, computed-aided diagnosis (CAD) systems are required to assist specialists for a fast, reliable diagnosis, allowing to reduce the workload and the associated costs. We hypothesize that the application of novel, automatic algorithms for fundus image analysis could contribute to the early diagnosis of DR. Consequently, the main objective of the present Doctoral Thesis is to study, design and develop novel methods based on the automatic analysis of fundus images to aid in the screening, diagnosis, and treatment of DR. In order to achieve the main goal, we built a private database and used five retinal public databases: DRIMDB, DIARETDB1, DRIVE, Messidor and Kaggle. The stages of fundus image processing covered in this Thesis are: retinal image quality assessment (RIQA), the location of the optic disc (OD) and the fovea, the segmentation of RLs and EXs, and the DR severity grading. RIQA was studied with two different approaches. The first approach was based on the combination of novel, global features. Results achieved 91.46% accuracy, 92.04% sensitivity, and 87.92% specificity using the private database. We developed a second approach aimed at RIQA based on deep learning. We achieved 95.29% accuracy with the private database and 99.48% accuracy with the DRIMDB database. The location of the OD and the fovea was performed using a combination of saliency maps. The proposed methods were evaluated over the private database and the public databases DRIVE, DIARETDB1 and Messidor. For the OD, we achieved 100% accuracy for all databases except Messidor (99.50%). As for the fovea location, we also reached 100% accuracy for all databases except Messidor (99.67%). The joint segmentation of RLs and EXs was accomplished by decomposing the fundus image into layers. Results were computed per pixel and per image. Using the private database, 88.34% per-image accuracy (ACCi) was reached for the RL detection and 95.41% ACCi for EX detection. An additional method was proposed for the segmentation of RLs based on superpixels. Evaluating this method with the private database, we obtained 84.45% ACCi. Results were validated using the DIARETDB1 database. Finally, we proposed a deep learning framework for the automatic DR severity grading. The method was based on a novel attention mechanism which performs a separate attention of the dark and the bright structures of the retina. The Kaggle DR detection dataset was used for development and validation. The International Clinical DR Scale was considered, which is made up of 5 DR severity levels. Classification results for all classes achieved 83.70% accuracy and a Quadratic Weighted Kappa of 0.78. The methods proposed in this Doctoral Thesis form a complete, automatic DR screening system, contributing to aid in the early detection of DR. In this way, diabetic patients could receive better attention for their ocular health avoiding vision loss. In addition, the workload of specialists could be relieved while healthcare costs are reduced.La retinopatía diabética (RD) es la complicación más común de la diabetes mellitus y una de las principales causas de ceguera prevenible en la población activa adulta. El diagnóstico precoz es primordial para prevenir la pérdida visual. Sin embargo, la RD es clínicamente asintomática hasta etapas avanzadas, cuando la visión ya está afectada. Por eso, los pacientes diabéticos deben someterse a exámenes oftalmológicos periódicos a través de programas de cribado. Tradicionalmente, estos programas están a cargo de especialistas y se basan de la inspección visual de retinografías. Sin embargo, este análisis manual requiere mucho tiempo y es costoso. Con la creciente incidencia de la diabetes y la escasez de recursos sanitarios, la detección precoz de la RD se hace inviable. Por esta razón, se necesitan sistemas de diagnóstico asistido por ordenador (CAD) que ayuden a los especialistas a realizar un diagnóstico rápido y fiable, que permita reducir la carga de trabajo y los costes asociados. El objetivo principal de la presente Tesis Doctoral es estudiar, diseñar y desarrollar nuevos métodos basados en el análisis automático de retinografías para ayudar en el cribado, diagnóstico y tratamiento de la RD. Las etapas estudiadas fueron: la evaluación de la calidad de la imagen retiniana (RIQA), la localización del disco óptico (OD) y la fóvea, la segmentación de RL y EX y la graduación de la severidad de la RD. RIQA se estudió con dos enfoques diferentes. El primer enfoque se basó en la combinación de características globales. Los resultados lograron una precisión del 91,46% utilizando la base de datos privada. El segundo enfoque se basó en aprendizaje profundo. Logramos un 95,29% de precisión con la base de datos privada y un 99,48% con la base de datos DRIMDB. La localización del OD y la fóvea se realizó mediante una combinación de mapas de saliencia. Los métodos propuestos fueron evaluados sobre la base de datos privada y las bases de datos públicas DRIVE, DIARETDB1 y Messidor. Para el OD, logramos una precisión del 100% para todas las bases de datos excepto Messidor (99,50%). En cuanto a la ubicación de la fóvea, también alcanzamos un 100% de precisión para todas las bases de datos excepto Messidor (99,67%). La segmentación conjunta de RL y EX se logró descomponiendo la imagen del fondo de ojo en capas. Utilizando la base de datos privada, se alcanzó un 88,34% de precisión por imagen (ACCi) para la detección de RL y un 95,41% de ACCi para la detección de EX. Se propuso un método adicional para la segmentación de RL basado en superpíxeles. Evaluando este método con la base de datos privada, obtuvimos 84.45% ACCi. Los resultados se validaron utilizando la base de datos DIARETDB1. Finalmente, propusimos un método de aprendizaje profundo para la graduación automática de la gravedad de la DR. El método se basó en un mecanismo de atención. Se utilizó la base de datos Kaggle y la Escala Clínica Internacional de RD (5 niveles de severidad). Los resultados de clasificación para todas las clases alcanzaron una precisión del 83,70% y un Kappa ponderado cuadrático de 0,78. Los métodos propuestos en esta Tesis Doctoral forman un sistema completo y automático de cribado de RD, contribuyendo a ayudar en la detección precoz de la RD. De esta forma, los pacientes diabéticos podrían recibir una mejor atención para su salud ocular evitando la pérdida de visión. Además, se podría aliviar la carga de trabajo de los especialistas al mismo tiempo que se reducen los costes sanitarios.Escuela de DoctoradoDoctorado en Tecnologías de la Información y las Telecomunicacione

Natural Parameterization

The objective of this project has been to develop an approach for imitating physical objects with an underlying stochastic variation. The key assumption is that a set of “natural parameters” can be extracted by a new subdivision algorithm so they reflect what is called the object’s “geometric DNA”. A case study on one hundred wheat grain crosssections (Triticum aestivum) showed that it was possible to extract thirty-six such parameters and to reuse them for Monte Carlo simulation of “new” stochastic phantoms which possessthe same stochastic behavior as the “original” cross-sections